Idiopathic osteonecrosis of the femoral head (ION) is an intractable disease of unknown etiology, associated with steroid administration and excessive alcohol intake, in which part of the femoral head necroses. There are said to be approximately 2200 new cases of ION countrywide yearly (Non-patent Reference 1). Peak onset occurs in relatively young people in their 30s to 40s. If the femoral head collapses, it causes severe pain and ADL restrictions, necessitating surgical treatment such as osteotomy and artificial hip joint replacement. The results of surgical treatment of ION have been extensively researched (Non-patent References 2 and 3), but there is few research on conservative treatments.
Fragility fractures based on osteoporosis have become a problem in recent years, and a variety of osteoporosis therapeutics are being developed. Bisphosphonates among them play a central role and actualize their effect by suppressing bone resorption by lowering the activity of osteoclasts. Administration of bisphosphonates as a conservative treatment of ION is reported to decrease the rate of femoral head collapse after ION onset (Non-patent References 4-7).
Parathyroid hormone (PTH) has the kidneys and bones as its main target organs and is a hormone that acts to raise the blood Ca concentration. Persistent elevation of PTH activity causes bone loss. However, intermittent administration of PTH is said to have the effect of increasing bone mass and preventing bone fractures, and intermittently administered PTH formulations have become available for use as osteoporosis therapeutics in recent years. These PTH formulations have a bone formation promoting action not seen with conventional osteoporosis therapeutics and are expected to serve as more potent osteoporosis therapeutics. PTH formulations have been approved as osteoporosis therapeutics, but efficacy has also been reported recently in the treatment of osteonecrosis of the jawbone and bone formation after periodontal surgery (Non-patent References 8 and 9). Animal studies suggest utility in bone formation surrounding implants and promotion of the healing of bone fractures (Non-patent References 10 and 11). The possibility of promoting the treatment of transient osteoporosis of the hip in the hip joint is also suggested (Non-patent Reference 12).
Experimental results on the suppressive effect on femoral head collapse have also been reported in ION, focusing on the bone formation promoting action of teriparatide (Non-patent Reference 15). This report took the difference in femoral head collapse values before and after administration using simple x-ray frontal views as the endpoint; the extent of suppression of progress of the stage was not evaluated. Furthermore, this report is a trial results report using alendronate as the control; the existence of a placebo control is unclear. The method of assigning teriparatide and alendronate is also unclear. In addition, this report does not disclose the dosage and administration of teriparatide. It is stated that teriparatide tended to suppress femoral head collapse progress in comparison to alendronate as the result, but no statistical superiority between the two groups was found.
Furthermore, the bone density and clinical course of 40 subjects administered 20 μg/day of teriparatide were also reported. Ten of them (25%) had a decrease in femoral bone density, and one is introduced as a case in which bilateral osteonecrosis of the femoral head developed, although the relationship to the drug is unclear (Non-patent Reference 16).
Moreover, teriparatide administration is reported to have an effect against osteonecrosis of the jawbone induced by bisphosphonates and denosumab (Non-patent References 17 and 18), but this report discloses nothing whatsoever about the effect of teriparatide on ION.